A POLH transcript with a short 30UTR enhances POLH expression and mediates cisplatin resistance

Jin Zhang, Wenqiang Sun, Cong Ren, Xiangmudong Kong, Wensheng Yan, Xinbin Chen

Research output: Contribution to journalArticle

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Abstract

Platinum-based anticancer drugs are widely used as a first-transcript with 427-nt 30UTR is responsible for high expression line drug for cancers, such as non–small cell lung carcinoma of PolH in various cisplatin-resistant lung and bladder cancer (NSCLC) and bladder cancer. However, the efficacy is limited cell lines. Importantly, loss of the short PolH transcript sig-due to intrinsic or acquired resistance to these drugs. DNA nificantly sensitizes cancer cells to cisplatin treatment. More-polymerase eta (PolH, Polh) belongs to the Y-family of DNA over, we found that miR-619 selectively inhibits the ability of polymerases and mediates DNA translesion synthesis, a major the long PolH transcript with 6245-nt 30UTR to produce PolH mechanism for DNA damage tolerance. Here, we showed that protein and, subsequently, PolH-dependent cell growth. a high level of PolH is associated with cisplatin resistance in Together, our data suggest that PolH expression is controlled lung and bladder cancer. Consistent with this, loss of PolH by APA and that the short PolH transcript produced by APA can markedly attenuates cisplatin resistance in both cisplatin-escape miR-619–mediated repression and, subsequently, con-sensitive and cisplatin-resistant lung cancer cells. Interestingly, fers PolH-mediated cisplatin resistance. we found that due to the presence of multiple polyadenylation sites, alternative polyadenylation (APA) produces three major Significance: A short PolH transcript produced by alterna-PolH transcripts with various lengths of 30untranslated region tive polyadenylation escapes repression by miR-619 and (30UTR; 427-/2516-/6245-nt). We showed that the short PolH confers resistance to cisplatin.

Original languageEnglish (US)
Pages (from-to)3714-3724
Number of pages11
JournalCancer Research
Volume79
Issue number14
DOIs
StatePublished - Jan 1 2019

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Cisplatin
Polyadenylation
Urinary Bladder Neoplasms
Lung Neoplasms
DNA
DNA-Directed DNA Polymerase
Platinum
Drug Resistance
Pharmaceutical Preparations
DNA Damage
Neoplasms
Carcinoma
Cell Line
Lung
Growth
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A POLH transcript with a short 30UTR enhances POLH expression and mediates cisplatin resistance. / Zhang, Jin; Sun, Wenqiang; Ren, Cong; Kong, Xiangmudong; Yan, Wensheng; Chen, Xinbin.

In: Cancer Research, Vol. 79, No. 14, 01.01.2019, p. 3714-3724.

Research output: Contribution to journalArticle

Zhang, Jin ; Sun, Wenqiang ; Ren, Cong ; Kong, Xiangmudong ; Yan, Wensheng ; Chen, Xinbin. / A POLH transcript with a short 30UTR enhances POLH expression and mediates cisplatin resistance. In: Cancer Research. 2019 ; Vol. 79, No. 14. pp. 3714-3724.
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